MC1 receptor
Target id: 282
Nomenclature: MC1 receptor
Family: Melanocortin receptors
Annotation status:
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GtoImmuPdb view: OFF : Currently no data for MC1 receptor in GtoImmuPdb
Contents:
- Gene and Protein Information
- Previous and Unofficial Names
- Database Links
- Natural/Endogenous Ligands
- Rank order lists
- Agonists
- Antagonists
- Transduction Mechanisms
- Tissue Distribution
- Expression Datasets
- Functional Assays
- Physiological Functions
- Phenotypes, Alleles and Disease Models
- Clinically-Relevant Mutations and Pathophysiology
- Biologically Significant Variants
- General Comments
- References
- Contributors
- How to cite this page
Gene and Protein Information  |
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| class A G protein-coupled receptor | ||||||
| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 7 | 317 | 16q24.3 | MC1R | melanocortin 1 receptor | 22 |
| Mouse | 7 | 315 | 8 E2 | Mc1r | melanocortin 1 receptor | 22 |
| Rat | 7 | 325 | 19q12 | Mc1r | melanocortin 1 receptor | |
| Previous and Unofficial Names |
| MSH-R | melanocortin 1 receptor (alpha melanocyte stimulating hormone receptor) |
| Database Links |
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| Specialist databases | |
| GPCRDB | mshr_human (Hs), mshr_mouse (Mm) |
| Other databases | |
| ChEMBL Target | 11869 (Hs), 12708 (Mm) |
| Ensembl Gene | ENSG00000258839 (Hs), ENSMUSG00000074037 (Mm), ENSRNOG00000038193 (Rn) |
| Entrez Gene | 4157 (Hs), 17199 (Mm), 292083 (Rn) |
| Human Protein Atlas | ENSG00000258839 (Hs) |
| KEGG Gene | hsa:4157 (Hs), mmu:17199 (Mm), rno:292083 (Rn) |
| OMIM | 155555 (Hs) |
| Orphanet | ORPHA139778 (Hs) |
| RefSeq Nucleotide | NM_002386 (Hs), NM_008559 (Mm) |
| RefSeq Protein | NP_002377 (Hs), NP_032585 (Mm) |
| UniProtKB | Q01726 (Hs), Q01727 (Mm) |
| Wikipedia | MC1R (Hs) |
| Natural/Endogenous Ligands |
| ACTH {Sp: Human} , ACTH {Sp: Mouse, Rat} |
| β-MSH {Sp: Human} |
| α-MSH {Sp: Human, Mouse, Rat} |
| γ-MSH {Sp: Human, Mouse, Rat} |
| β-MSH {Sp: Mouse} , β-MSH {Sp: Rat} |
| Comments: α-MSH is the principal endogenous agonist. Endogenous antagonists are agouti and agouti-related protein. For representations of the rodent orthologues of these peptides see agouti (mouse), agouti (rat) and agouti-related protein (mouse). |
| Potency order of endogenous ligands (Human) |
| α-MSH (POMC, P01189) > β-MSH (POMC, P01189) > ACTH (POMC, P01189), γ-MSH (POMC, P01189) |
Download all structure-activity data for this target as a CSV file 
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| The human MC1 compared to the mouse MC1 is "supersensitive" to the melanocortin peptides [20]. A selective MC1 receptor agonist with nanomolar potency has recently been described [11]. cAMP but no binding data were published. Ro27-3225 is a selective MC1R and MC4R agonist [2]. cAMP but no binding data were published. [125I]NDP-MSH, [125I]MT-II, [125I]SHU9119, [125I]Nle7-α-MSH are common radioligands used to study MC1, 3, 4 and MC5. |
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| Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
| Gs family | Adenylate cyclase stimulation |
| References: 20 | |
| Secondary Transduction Mechanisms |
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| Transducer | Effector/Response |
| G protein (identity unknown) | Other - See Comments |
| Comments: Melanocortin activation of the murine MC1R mobilizes intracellular calcium via an incompletely understood pathway. | |
| References: 21 | |
| Tissue Distribution
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| Expression Datasets |
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| Functional Assays
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| Physiological Functions
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| Phenotypes, Alleles and Disease Models
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| Clinically-Relevant Mutations and Pathophysiology
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| Biologically Significant Variants
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| Biologically Significant Variant Comments | ||||||||
| Common variations (polymorphisms) in the MC1R gene are associated with normal differences in skin and hair color. The MC1 receptor regulates the balance between eumelanin (associated with black hair and dark skin that tans easily) and pheomelanin (associated with fair hair, and easily burnt skin on UV exposure) production by melanocytes. MC1 receptor activation favours the production of eumelanin, whereas inactivating variants lead to pheomelanin production. Inactivating receptor polymorphisms are most common in people with red hair, fair skin, freckles, and an increased sensitivity to sun exposure. Inactivating mutations are also associated with increased risk of developing skin cancers, since the inability to produce sufficient eumelanin leaves fair skin more vulnerable to damage from sun exposure. |
| General Comments |
| Bioassays based on frog and lizard skin are also used. [5] |
References
1. Al-Obeidi F, Hruby VJ, Castrucci AM, Hadley ME. (1989) Design of potent linear α-melanotropin 4-10 analogues modified in positions 5 and 10. J Med Chem., 32: 174-179. [PMID:2535874]
2. Benoit SC, Schwartz MW, Lachey JL, Hagan MM, Rushing PA, Blake KA, Yagaloff KA, Kurylko G, Franco L, Danhoo W, Seeley RJ. (2000) A novel selective melanocortin-4 receptor agonist reduces food intake in rats and mice without producing aversive consequences. J. Neurosci., 20: 3442-3448. [PMID:10777807]
3. Bohm M, Eickelmann M, Li Z, Schneider SW, Oji V, Diederichs S, Barsh GS, Vogt A, Stieler K, Blume-Peytavi U, Luger TA. (2005) Detection of functionally active melanocortin receptors and evidence for an immunoregulatory activity of {alpha}-melanocyte-stimulating hormone in human dermal papilla cells. Endocrinology,: -. [PMID:16081629]
4. Boston BA, Cone RD. (1996) Characterization of melanocortin receptor subtype expression in murine adipose tissues and in the 3T3-L1 cell line. Endocrinology, 137: 2043-2050. [PMID:8612546]
5. Castrucci AM, Hadley ME, Hruby VJ. (1984) Melanotropin bioassays: in vitro and in vivo comparisons. Gen Comp Endocrinol., 55: 104-111. [PMID:6611282]
6. Catania A, Rajora N, Capsoni F, Minonzio F, Star RA, Lipton JM. (1996) The neuropeptide alpha-MSH has specific receptors on neutrophils and reduces chemotaxis in vitro. Peptides., 17: 675-679. [PMID:8804079]
7. Chhajlani V. (1996) Distribution of cDNA for melanocortin receptor subtypes in human tissues. Biochem Mol Biol Int., 38: 73-80. [PMID:8932521]
8. Chhajlani V, Wikberg JES. (1992) Molecular cloning and expression of the human melanocyte stimulating hormone receptor cDNA. FEBS Lett., 309: 417-420. [PMID:8706868]
9. Dinulescu DM, Cone RD. (2000) Agouti and agouti-related protein: Analogies and contrasts. J. Biol. Chem., 275: 6695-6698. [PMID:10702221]
10. Hartmeyer M, Scholzen T, Becher E, Bhardwaj RS, Schwarz T, Luger TA. (1997) Human dermal microvascular endothelial cells express the melanocortin receptor type 1 and produce increased levels of IL-8 upon stimulation with alpha-melanocyte-stimulating hormone. J Immunol., 159: 1930-1937. [PMID:9257858]
11. Herpin TF, Yu G, Carlson KE, Morton GC, Wu X, Kang L, Tuerdi H, Khanna A, Tokarski JS, Lawrence RM, Macor JE. (2003) Discovery of tyrosine-based potent and selective melanocortin-1 receptor small-molecule agonists with anti-inflammatory properties. J. Med. Chem., 46: 1123-1126. [PMID:12646021]
12. Hruby VJ, Lu D, Sharma SD, Castrucci AL, Kesterson RA, al-Obeidi FA, Hadley ME, Cone RD. (1995) Cyclic lactam α-melanotropin analogues of Ac-Nle4-c[Asp4,D-Phe7, Lys10] α-MSH(4-10)-NH2with bulky aromatic amino acids at position 7 show high antagonist potency and selectivity at specific melanocortin receptors. J. Med. Chem., 38: 3454-3461. [PMID:7658432]
13. Jayawickreme CK, Jayawickreme SP, Lerner MR. (1998) Functional screening of multiuse peptide libraries using melanophore bioassay. Methods Mol. Biol. , 87: 119-128. [PMID:9523265]
14. Kask A, Mutulis F, Muceniece R, Pähkla R, Mutule I, Wikberg JE, Rägo L, Schiöth HB. (1998) Discovery of a novel superpotent and selective melanocortin-4 receptor antagonist (HS024): evaluation in vitro and in vivo. Endocrinology, 139: 5006-5014. [PMID:9832440]
15. Kiefer LL, Veal JM, Mountjoy KG, Wilkison WO. (1998) Melanocortin receptor binding determinants in the agouti protein. Biochemistry, 37 (4): 991-7. [PMID:9454589]
16. Kopanchuk S, Veiksina S, Petrovska R, Mutule I, Szardenings M, Rinken A, Wikberg JE. (2005) Co-operative regulation of ligand binding to melanocortin receptor subtypes: evidence for interacting binding sites. Eur J Pharmacol, 512: 85-95. [PMID:15840392]
17. Kumar KG, Sutton GM, Dong JZ, Roubert P, Plas P, Halem HA, Culler MD, Yang H, Dixit VD, Butler AA. (2009) Analysis of the therapeutic functions of novel melanocortin receptor agonists in MC3R- and MC4R-deficient C57BL/6J mice. Peptides, 30 (10): 1892-900. [PMID:19646498]
18. Lu D, Willard D, Patel IR, Kadwell S, Overton L, Kost T, Luther M, Chen W, Woychik RP, Wilkison WO et al.. (1994) Agouti protein is an antagonist of the melanocyte-stimulating hormone receptor. Nature, 371: 799-802. [PMID:7935841]
19. MacNeil DJ, Howard AD, Guan X, Fong TM, Nargund RP, Bednarek MA, Goulet MT, Weinberg DH, Strack AM, Marsh DJ, Chen HY, Shen CP, Chen AS, Rosenblum CI, MacNeil T, Tota M, MacIntyre ED, Van der Ploeg LH. (2002) The role of melanocortins in body weight regulation: opportunities for the treatment of obesity. Eur. J. Pharmacol., 440: 141-157. [PMID:12007532]
20. Mountjoy KG. (1994) The human melanocyte stimulating hormone receptor has evolved to become "super-sensitive" to melanocortin peptides. Mol. Cell Endocrinol., 102: 7-11. [PMID:8187950]
21. Mountjoy KG, Kong PL, Taylor JA, Willard DH, Wilkison WO. (2001) Melanocortin receptor-mediated mobilization of intracellular free calcium in HEK293 cells. Physiol. Genomics, 5: 11-19. [PMID:11161002]
22. Mountjoy KG, Robbins LS, Mortrud MT, Cone RD. (1992) The cloning of a family of genes that encode the melanocortin receptors. Science, 257: 1248-1251. [PMID:1325670]
23. Robbins LS, Nadeau JH, Johnson KR, Kelly MA, Roselli-Rehfuss L, Baack E, Mountjoy KG, Cone RD. (1993) Pigmentation phenotypes of variant extension locus alleles result from point mutations that alter MSH receptor function. Cell., 72: 827-834. [PMID:8458079]
24. Schioth HB, Muceniece R, Mutulis F, Bouifrouri AA, Mutule I, Wikberg JE. (1999) Further pharmacological characterization of the selective melanocortin 4 receptor antagonist HS014: comparison with SHU9119. Neuropeptides, 33: 191-196. [PMID:10657491]
25. Schioth HB, Muceniece R, Wikberg JE, Chhajlani V. (1995) Characterisation of melanocortin receptor subtypes by radioligand binding analysis. Eur J Pharmacol, 288 (3): 311-317. [PMID:7774675]
26. Smith AI, Funder JW. (1988) Proopiomelanocortin processing in the pituitary, central nervous system, and peripheral tissues. Endocr. Rev., 9: 159-179. [PMID:3286233]
27. Star RA, Rajora N, Huang J, Stock RC, Catania A, Lipton JM. (1995) Evidence of autocrine modulation of macrophage nitric oxide synthase by alpha-melanocyte-stimulating hormone. Proc Natl Acad Sci U S A., 92: 8016-8020. [PMID:7544012]
28. Szardenings M, Muceniece R, Mutule I, Mutulis F, Wikberg JE. (2000) New highly specific agonistic peptides for human melanocortin MC1 receptor. Peptides., 21: 239-243. [PMID:10764951]
29. Tan CP, McKee KK, Weinberg DH, MacNeil T, Palyha OC, Feighner SD, Hreniuk DL, Van Der Ploeg LH, MacNeil DJ, Howard AD. (1999) Molecular analysis of a new splice variant of the human melanocortin-1 receptor. FEBS Lett., 451: 137-141. [PMID:10371153]
30. Wikberg JE. (1999) Melanocortin receptors: perspectives for novel drugs. Eur. J. of Pharmacol., 375: 295-310. [PMID:10443584]
31. Yang Y-K Dickinson C, Lae Y-M, Li J-Y, Ira Gantz I. (2001) Functional properties of an agouti signaling protein variant and binding characteristics of its cognate radioligand. Am. J. Physiol. Regul. Integr. Comp. Physiol., 281: 1877-1886. [PMID:11705773]
32. Yang YK, Ollmann MM, Wilson BD, Dickinson C, Yamada T, Barsh GS, Gantz I. (1997) Effects of recombinant agouti-signaling protein on melanocortin action. Mol. Endocrinol. , 11: 274-280. [PMID:9058374]
How to cite this page
Tung M. Fong, Helgi Schiöth, Ira Gantz, Roger D. Cone, Sadaf Farooqi, Carrie Haskell-Luevano, Victor J. Hruby, Kathleen G. Mountjoy, Jeffrey B. Tatro, Jarl E. S. Wikberg.
Melanocortin receptors: MC1 receptor. Last modified on 20/02/2018. Accessed on 17/01/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=282.
